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Case report: mismatch repair proficiency and microsatellite stability in gastric cancer may not predict programmed
Kuo-Hsing Chen1,2,3, Chang-Tsu Yuan4, Li-Hui Tseng5
1Department of Oncology, National Taiwan University Hospital, 7, Chun-Shan S Rd, Taipei, 10002, Taiwan.
Background:
Anti-programmed death-1 therapy has poor efficacy in mismatch repair-proficient (pMMR) colorectal cancers; however, its efficacy in pMMR gastric cancers remains undetermined. Here, we report the case of a patient with pMMR and microsatellite-stable gastric cancer who exhibited a partial response to salvage anti-programmed death-1 therapy with pembrolizumab.
Case Presentation:
Initially, the patient underwent subtotal gastrectomy 4 years ago for early-stage gastric cancer (pT1bN2M0, stage IIA). Immunohistochemical analysis of the tumor revealed strongly positive for HER2/neu. He had received trastuzumab plus pertuzumab, cisplatin, and capecitabine for recurrent tumors since September 2014 for 15 cycles. Disease progression of gastric cancer was found in August 2015. Since September 2015, the patient has received pembrolizumab monotherapy (200 mg as a fixed dose, every 3 weeks) for 3 months and the repeat computed tomography demonstrated a confirmed partial response. The plasma carcinoembryonic antigen also decreased dramatically. Both immunohistochemistry and a polymerase chain reaction-based method revealed that the patient had pMMR gastric cancer.
Conclusions:
This case report provides the first report that mismatch repair-proficient and microsatellite-stable gastric cancers can respond well to anti-PD-1 monotherapy and indicates both markers may not sufficiently be predictive of anti-PD-1 therapy resistance in gastric cancer.
Insights
This case study shows a patient with mismatch repair-proficient (pMMR) gastric cancer responding to anti-programmed death-1 (anti-PD-1) therapy. This suggests pMMR status may not predict resistance to immunotherapy in gastric cancer.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Anti-programmed death-1 (anti-PD-1) therapy shows limited efficacy in mismatch repair-proficient (pMMR) colorectal cancers.
- The efficacy of anti-PD-1 therapy in pMMR gastric cancer is not well-established.
Observation:
- A patient with pMMR and microsatellite-stable gastric cancer received salvage anti-PD-1 therapy with pembrolizumab.
- The patient had previously undergone gastrectomy and received HER2-targeted therapy and chemotherapy for recurrent disease.
- Computed tomography and plasma carcinoembryonic antigen levels indicated a partial response to pembrolizumab after 3 months.
Findings:
- The patient's pMMR gastric cancer exhibited a partial response to pembrolizumab monotherapy.
- Immunohistochemistry and PCR confirmed the tumor was pMMR and microsatellite-stable.
Implications:
- This case suggests that pMMR and microsatellite-stable gastric cancers can respond to anti-PD-1 monotherapy.
- These markers may not be sufficient to predict resistance to anti-PD-1 therapy in gastric cancer.
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